Chromosome cohesion decreases in human eggs with advanced maternal age.

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Chromosome cohesion decreases in human eggs with advanced maternal age.

Aging Cell. 2012 Jul 23;

Authors: Duncan FE, Hornick JE, Lampson MA, Schultz RM, Shea LD, Woodruff TK

Abstract

Aneuploidy in human eggs increases with maternal age and can result in infertility, miscarriages, and birth defects. The molecular mechanisms leading to aneuploidy, however, are largely unknown especially in the human where eggs are exceedingly rare and precious. We obtained human eggs from subjects ranging from 16.4 to 49.7 years old following in vitro maturation of oocyte-cumulus-complexes (OCCs) isolated directly from surgically-removed ovarian tissue. Whereas maternal age negatively impacted the total number of OCCs collected per subject, it did not appear to impact the ability of the gamete to resume meiosis and form a mature egg. We used a subset of these eggs to investigate how age-associated aneuploidy occurs in the human. The inter-kinetochore distance between sister chromatids increased significantly with maternal age, indicating weakened cohesion. Moreover, we observed unpaired sister chromatids from females of advanced age. We conclude that loss of cohesion with increasing maternal age likely contributes to the well-documented increased incidence of aneuploidy. © 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
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PMID: 22823533 [PubMed - as supplied by publisher]